Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta-analysis

Br J Clin Pharmacol. 2013 Sep;76(3):348-57. doi: 10.1111/bcp.12149.

Abstract

Aims: To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).

Methods: Several databases were searched, including Pubmed, Embase and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned axitinib at a starting dose of 5 mg orally twice daily with data on hypertension available. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.

Results: A total of 1908 patients from 10 clinical trials were included. The overall incidences of all grade and high grade hypertension in cancer patients were 40.1% (95% CI 30.9, 50.2%) and 13.1% (95% CI 6.7, 24%). The use of axitinib was associated with significantly increased risk of all grade (RR 3.00, 95% CI 1.29, 6.97, P = 0.011) and high grade hypertension (RR 1.71, 95% CI 1.21, 2.43, P = 0.003). The risk of axitinib associated all grade and high grade hypertension in renal cell carcinoma (RCC) was significantly higher than that in non-RCC. Additionally, the risk of hypertension with axitinib was substantially higher than other approved VEGFR-TKIs, while the risk of all grade hypertension with axitinib was similar to pazopanib (RR 1.05; 95% CI 0.95-, 1.17, P = 0.34).

Conclusions: While sharing a similar spectrum of target receptors with other VEGFR-TKIs, axitinib is associated with an unexpectedly high risk of developing hypertension. Close monitoring and appropriate management for hypertension are recommended during the treatment.

Keywords: axitinib; hypertension; meta-analysis; tyrosine kinase inhibitor.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Axitinib
  • Clinical Trials as Topic
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / epidemiology
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects*
  • Imidazoles / therapeutic use
  • Incidence
  • Indazoles / administration & dosage
  • Indazoles / adverse effects*
  • Indazoles / therapeutic use
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Risk

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Indazoles
  • Protein Kinase Inhibitors
  • Axitinib
  • Receptors, Vascular Endothelial Growth Factor